Cellular probes designed to monitor electrophysiological events play an important role in experimental cell biology and pharmacology. In modern electrophysiology, electrolyte-filled glass micropipettes are utilized to access intracellular domains in order to measure how a stimulus affects the flow of ions through or changes the electrical potential across the cell membrane. Traditionally, electrical measurements in small cells are measured with either large-tipped, glass micropipettes filled with intracellular solution or fine-tipped, glass micropipettes filled with highly concentrated salt solution.
While versatile and widely-used, the patch-clamp technique ruptures the cell membrane and alters the internal milieu of a cell, preventing both long-term and repetitive monitoring. In contrast, fine-tipped, glass microelectrodes are less intrusive and therefore are more likely to spare a cell from irreparable damage. However, cell damage may still occur during prolonged measurement when the high-concentration electrolyte contained in the pipette's lumen diffuses into the cell. Problems that impact intracellular recording techniques and degrade recording performance include clogging of the electrode tip, collecting debris at the tip during probe penetration, and tip damage upon approaching and penetrating the cell.
To address some of these shortcomings, ohmic nanoelectrodes for intracellular recording have been proposed by others. Ohmic nanoelectrodes penetrate through tissue and into cells, measure electrical signals without altering cell characteristics. These devices, however, are not capable of both intracellular delivery and electrical recording. Thus, there is a need in the art for devices and methods for monitoring intracellular conditions while also having the ability to deliver agents to the intracellular region.